Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1.
The COOH-terminal A168-170 region of the giant sarcomeric protein titin interacts with muscle-specific RING finger-1 (MURF-1). To investigate the functional significance of this interaction, we expressed green fluorescent protein fusion constructs encoding defined fragments of titin's M-line region and MURF-1 in cardiac myocytes. Upon expression of MURF-1 or its central ... region (containing its titin-binding site), the integrity of titin's M-line region was dramatically disrupted. Disruption of titin's M-line region also resulted in a perturbation of thick filament components, but, surprisingly, not of the NH2-terminal or I-band regions of titin, the Z-lines, or the thin filaments. This specific phenotype also was caused by the expression of titin A168-170. These data suggest that the interaction of titin with MURF-1 is important for the stability of the sarcomeric M-line region.MURF-1 also binds to ubiquitin-conjugating enzyme-9 and isopeptidase T-3, enzymes involved in small ubiquitin-related modifier-mediated nuclear import, and with glucocorticoid modulatory element binding protein-1 (GMEB-1), a transcriptional regulator. Consistent with our in vitro binding data implicating MURF-1 with nuclear functions, endogenous MURF-1 also was detected in the nuclei of some myocytes. The dual interactions of MURF-1 with titin and GMEB-1 may link myofibril signaling pathways (perhaps including titin's kinase domain) with muscle gene expression.
Mesh Terms:
Animals, Carbon-Nitrogen Lyases, Cell Nucleus, Cells, Cultured, Chick Embryo, DNA-Binding Proteins, Gene Expression, Green Fluorescent Proteins, Humans, Indicators and Reagents, Ligases, Luminescent Proteins, Molecular Sequence Data, Muscle Fibers, Skeletal, Muscle Proteins, Myocardium, Myofibrils, Protein Kinases, Rats, Sarcomeres, Transcription Factors, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Animals, Carbon-Nitrogen Lyases, Cell Nucleus, Cells, Cultured, Chick Embryo, DNA-Binding Proteins, Gene Expression, Green Fluorescent Proteins, Humans, Indicators and Reagents, Ligases, Luminescent Proteins, Molecular Sequence Data, Muscle Fibers, Skeletal, Muscle Proteins, Myocardium, Myofibrils, Protein Kinases, Rats, Sarcomeres, Transcription Factors, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
J. Cell Biol.
Date: Apr. 01, 2002
PubMed ID: 11927605
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